Our current working hypothesis is that alterations in lipoprotein lipase activity either constitute or signal the onset of the inborn error of metabolism leading to this genetic form of obesity. Over the next year we intend to continue our examination of these early factors contributing to the development of the syndrome. We expect to delineate the developmental pattern of both plasma and pancreatic IRI during the postnatal period in lean and preobese rats. Two other major factors, serum lipoproteins and muscle protein synthesis will also be examined. We are currently trying to perfect a micro assay for plasma lipoproteins for use in the young rat. In order to establish that the severely compromised muscle growth apparent in the obese during chronic food restriction shown in our previously reported work is due to deprivation of muscle by adipose tissue rather than a problem in muscle per se, we are examining amino acid incorporation into muscle protein in lean and preobese rats. The results of these "prospective" studies should enable us to clearly define the temporal sequence of early events necessary for the obese syndrome expression.